There are more than a hundred types of peripheral neuropathy, including mononeuropathies and polyneuropathies. These include damage to the axons, or to the myelin sheath, or both.

The causes may be classified as:

Traumatic injury

Accidents, including vehicle accidents, sports accidents, surgical errors or complications.

Repeated stress injury, such as entrapment neuropathy, where a nerve is compressed within a bony or ligamentous tunnel. This is the result of the same joint repeating the same activity too many times, or even too forcefully, causing irritation by the rubbing of the soft tissues around the joint against the bone.

The outcome is inflammation and swelling of the tendons or ligaments, reducing the space available for the nerves to pass through, and compressing them. This is typically seen in carpal tunnel syndrome.

Systemic diseases manifesting with focal peripheral neuropathy

Metabolic or endocrine diseases such as diabetes mellitus, liver disease, hypothyroidism or acromegaly.

• In diabetes, abnormal glucose metabolism leads to a reduced nutrient supply, and a buildup of toxins, causing nerve damage.
• Liver disease leads to chemical alterations of the blood, disturbing normal nerve conduction.
• Hypothyroidism leads to slowing of metabolism, retention of fluid by the body, and swelling of the tissues, which can put pressure on the nerves.
• Increased growth hormone production in acromegaly causes abnormal bone growth, with joint enlargement, entrapping the nerves.

Vasculopathy, as in diabetes mellitus, or vasculitis.

• Here the main pathology is due to the impairment of oxygen supply to the peripheral nerves, which causes hypoxic damage to the nerves. Thus in vasculitis, multiple nerves may be affected by ischemic damage in different areas, which is called mononeuritis multiplex.

Autoimmune diseases

Here the overactive immune system attacks various cross-reactive body tissues, leading to various types of damage, including neuropathy. The common autoimmune diseases that manifest with peripheral neuropathy are Sjogren’s syndrome, systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA).

The occurrence of inflammation around a nerve may involve the nerve as well, causing it to become inflamed. Another mechanism is by the destruction of various joints and soft tissues, entrapping nerves in the resulting fibrous scar, deformity or immobile joint. Many chronic autoimmune diseases show waxing and waning of their activity.

Guillain-Barre syndrome is an acute autoimmune demyelinating condition, usually following viral infections, which causes the sudden onset of acute neuropathy, and may sometimes be life-threatening in its severity.

Chronic inflammatory demyelination can result in polyneuropathy, of both motor and sensory nerves. However, multifocal motor neuropathy affects only the motor nerves, either in an acute or chronic manner.

Renal disease

Here, the buildup of urea and other toxic wastes due to failure of filtration and excretion by the kidneys can affect nerve metabolism, and lead to permanent nerve damage.

Tumors

These can compress the nerves from outside, or destroy the nerve by growing into them, or originate from the nerve cells themselves.

Tumors sometimes provoke paraneoplastic syndromes, which are caused not by the primary mechanical effects of the tumor but by the immune response attacking other organs, causing degeneration, including nerve damage.

Another indirect means of tumor-induced neuropathy is following chemotherapy or radiation for a cancerous growth.

Neuromas are benign but painful tumors which develop from a site where a nerve was severed by trauma. They consist of a ball of regenerating axons. These may involve nearby nerves in their tangled growth, causing damage and pain.

Infections

Many viruses cause damage to sensory nerves, like the infamous zoster virus, causing jolts of intense pain. These also include cytomegalovirus (CMV), the Epstein-Barr virus (EBV), the HIV virus, and the herpes simplex virus (HSV). Lyme disease caused by Rickettsieae, and bacterial diseases such as leprosy and diphtheria, are also associated with widespread nerve damage.

Toxins, drugs and substance abuse

Chemotherapy is well known to produce peripheral neuropathy, and almost a third of patients on chemotherapy discontinue it because of this intolerable side effect. Anti-retroviral therapy drugs, anticonvulsants like phenytoin sodium, and some drugs used to control blood pressure such as aminodarone may also cause peripheral neuropathy. This type is usually temporary and improves when the offending drug is removed.

Lead, mercury and arsenic are well-known heavy metal poisons whose effects include nerve damage.

Alcohol abuse is a cause of permanent nerve damage, both directly as well as due to the induced deficiency of vitamin B1, B12, and folate which are important in nerve function and structure.

Genetic factors

Some mutations cause neuropathies, the milder ones in adulthood, but the more severe ones in infancy or childhood. Charcot-Marie-Tooth disease is a term for a varied group of diseases that is inherited, and cause degeneration of axons and their myelin sheaths. Prominent manifestations include atrophy of lower limb muscles, loss of tendon reflexes and sensory loss over the lower limbs.